6-OXO-NUCLEOSIDES USEFUL AS IMMUNOSUPPRESSANTS

Abstract: The present invention relates to certain novel 6-oxo-nucleosides which are useful as immunosuppressants and a process of preparing such compounds.

Description: 6-0X0-NUCLE0SIDES USEFUL AS IMMUNOSUPPRESSANTS FIELD OF THE INVENTION The present invention relates to certain novel 6-oxo- nucleosides which are useful as immunosuppressants and a process of preparing such compounds. BACKGROUND OF THE INVENTION Immunity is concerned with the recognition and disposal of foreign antigenic material which is present in the body. Typically the antigens are in the form of particulate matter (i.e., cells, bacteria, etc.) or large protein or polysaccharide molecules which are recognized by the immune system as being "non-self", i.e., detectably different or foreign from the animals own constituents. Potential antigens can be a variety of substances, often proteins, which are most frequently located on the outer surfaces of cells. For example, potential antigens can be found on pollen grains, tissue grafts, animal parasites, viruses, and bacteria. Once the antigenic material is recognized as "non-self" by the immune system, natural (non-specific) and/or adaptive immune responses can be initiated and maintained by the action of specific immune cells, antibodies and the complement system. Under certain conditions, including in certain disease states, an animal's immune system will recognize its own constituents as "non- self" and initiate an immune response against "self" material . An immune response can be carried out by the immune system by means of natural or adaptive mechanisms, each of which are composed of both cell-mediated and humoral elements. Natural mechanisms for immune response refer to those mechanisms involved in essentially non-specific immune reactions which involve the complement system and myeloid cells alone, such as macrophages, mast cells and polymorphonuclear leukocytes .(PMN) , in reacting to certain bacteria, viruses, tissue damage and other antigens. These natural mechanisms provide what is referred to as natural immunity. Adaptive mechanisms for immune response refer to those mechanisms which are mediated by lymphocytes (T and B cells) and antibodies which can respond selectively to thousands of different materials recognized as "non-self". These adaptive mechanisms provide what is referred to as adaptive immunity and lead to a specific memory and a permanently altered pattern of response in adaptation to the animal's own environment. Adaptive immunity can be provided by the lymphocytes and antibodies alone or, more commonly, can be provided by the interaction of lymphocytes and antibodies with the complement system and myeloid cells of the natural mechanisms of immunity. The antibodies provide the humoral element of the adaptive immune response and the T-cells provide the cell-mediated element of the adaptive immune response. Natural mechanisms of immune response involve phagocytosis by macrophages and PMN whereby foreign material or antigen is engulfed and disposed of by these cells. In addition, macrophages can kill some foreign cells through its cytotoxic effects. The complement system which is also involved in natural immunity is made up of various peptides and enzymes which can attach to foreign material or antigen and thereby promote phagocytosis by macrophages and PMN, or enable cell lysis or inflammatory effects to take place. Adaptive mechanisms of immune response involve the actions against specific antigens of antibody secreted by B- lymphocytes (or B-cells) as well as the actions of various T-lymphocytes (or T-cells) on a specific antigen, on B- cells, on other T-cells and on macrophages. Antibodies, which are responsible for the humoral aspect of adaptive immunity, are serum globulins secreted by B- cells with a wide range of specificity for different antigens. Antibodies are secreted in response to the recognition of specific antigens and provide a variety of protective responses. Antibodies can bind to and neutralize bacterial toxins and can bind to the surface of viruses, bacteria, or other cells recognized as "non-self" and thus promote phagocytosis by PMN and macrophages. In addition, antibodies can activate the complement system which further augments the immune response against the specific antigen. Lymphocytes are small cells found in the blood which circulate from the blood, through the tissues, and back to the blood via the lymph system. There are two major subpopulations of lymphocytes called B-cells and T-cells. B-cells and T-cells are both derived from the same lymphoid stem cell with the B-cells differentiating in the bone marrow and the T-cells differentiating in the thymus. The lymphocytes possess certain restricted receptors which permit each cell to respond to a specific antigen. This provides the basis for the specificity of the adaptive immune response. In addition, lymphocytes have a relatively long lifespan and have the ability to proliferate clonally upon receiving the proper signal. This property provides the basis for the memory aspect of the adaptive immune response. B-cells are the lymphocytes responsible for the humoral aspect of adaptive immunity. In response to recognition of a specific foreign antigen, a B-cell will secrete a specific antibody which binds to that specific antigen. The antibody neutralizes the antigen, in the case of toxins, or promotes phagocytosis, in the case of other antigens. Antibodies also are involved in the activation of the complement system which further escalates the immune response toward the invading antigen. T-cells are the lymphocytes responsible for the cell- mediated aspect of adaptive immunity. There are three major types of T-cells, i.e., the Cytotoxic T-cells, Helper T- cells and the Suppressor T-cells. The Cytotoxic T-cells detects and destroys cells infected with a specific virus antigen. Helper T-cells have a variety of regulatory functions. Helper T-cells, upon identification of a specific antigen, can promote or enhance an antibody response to the antigen by the appropriate B-cell and it can promote or enhance phagocytosis of the antigen by macrophages. Suppressor T-cells have the effect of suppressing an immune response directed toward a particular antigen. T cells recognize antigen via a unique membrane receptor: the T cell antigen receptor (TCR). The TCR can recognize antigen only in association with cell surface proteins known as major histocompatibility complex (MHC) molecules. In response to antigen presented by MHC class II molecules, T helper cells secrete a variety of soluble factors, collectively known as lymphokines. Lymphokines play an essential role in the activation, differentiation, and expansion of all the cells of the immune response. In contrast to the T helper cell, the T cytotoxic cell responds to antigen in the context of MHC class I molecules. Cytotoxic T lymphocytes, once activated, can eliminate cells displaying a specific antigen derived from a virus, tumor cell, or foreign tissue graft. The cell-mediated immune response is controlled and monitored by the T-cells through a variety of regulatory messenger compounds secreted by the myeloid cells and the lymphocyte cells. Through the secretion of these regulatory messenger compounds, the T-cells can regulate the proliferation and activation of other immune cells such as B-cells, macrophages, PMN and other T-cells. For example, upon binding a foreign antigen, a macrophage or other antigen presenting cell can secrete interleukin-1 (IL-1) which activates the Helper T-cells. T-cells in turn secrete certain lymphokines, including interleukin-2 (IL-2) and γ- interferon, each of which have a variety of regulatory effects in the cell-mediated immune response. Lymphokines are a large family of molecules produced by T-cells (and sometimes B-cells) including IL-2, which promotes the clonal proliferation of T- cells; MAF or macrophage activation factor, which increases many macrophage functions including phagocytosis, intracellular killing and secretion of various cytotoxic factors; NAF or neutrophil activation factor, which increases many functions of the PMN including phagocytosis, oxygen radical production, bacterial killing, enhanced chemotaxis and enhanced cytokine production; MIF or macrophage migration factor, which by restricting the movement of macrophages, concentrates them in the vicinity of the T-cell; γ-interferon, which is produced by the activated T-cell and is capable of producing a wide range of effects on many cells including inhibition of virus replication, induction of expression of class II histocompatibility molecules allowing these cells to become active in antigen binding and presentation, activation of macrophages, inhibition of cell growth, induction of differentiation of a number of myeloid cell lines. Mononuclear phagocytic macrophages are widely distributed throughout the body and display great structural and functional heterogeneity. Macrophages are derived from circulating monocytes which migrate into extravascular tissues. The migration of peripheral blood monocytes involves adherence to the endothelium, migration between endothelial cells, and subsequently movement through subendothelial structures. Adherence of monocytes to endothelium involves high molecular weight glycoproteins, such as lymphocyte function-associates antigen 1 (LFA-1; CDlla/CD18), which interacts with intercellular adhesion molecule-1 (ICAM-1; CD54) present on vascular endothelial cells. Monocytes and macrophages produce a variety of pro- inflammatory mediators (cytokines), such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF). These cytokines have numerous effects on many cells within and outside the immune system, such as promoting activation, differentiation, expansion, or apoptosis. In addition, cytokines such as IL-1 increase the expression of adhesion molecules like ICAM-1 and greatly facilitate monocyte migration to the inflammatory site. Furthermore, the monocyte/macrophage is one of the major types of antigen presenting cells required for T helper cell activation. Activated macrophages and PMNs, which provide an enhanced immune response as part of the cell-mediated adaptive immunity, are characterized as having increased production of reactive oxygen intermediates. This increased production of reactive oxygen intermediates, or respiratory burst, is known as "priming". Certain lymphokines, such as γ-interferon, trigger this respiratory burst of reactive oxygen intermediates in macrophages and PMNs. Thus, lymphokines, such as γ-interferon, which are secreted by the T-cells provide an activation of these macrophages and PMNs which results in an enhanced cell-mediated immune response. The immune response can provide an immediate or a delayed type of response. Delayed-type hypersensitivity is an inflammatory reaction which occurs in immune reactive patients within 24-48 hours after challenge with antigen and is the result primarily of a cell-mediated immune response. In contrast, immediate-type hypersensitivity, such as that seen in anaphylactic or Arthus reactions, is an inflammatory reaction which occurs in immune reactive patients within minutes to a few hours after challenge with antigen and is the result primarily of humoral or antibody-mediated immune response. The ability of the immune system, and in particular the cell-mediated immune system, to discriminate between "self" and "non-self" antigens is vital to the functioning of the immune system as a specific defense against invading microorganisms. "Non-self" antigens are those antigens or substances in the body which are detectably different or foreign from the animals own constituents. "Self" antigens are those antigens which are not detectably different or foreign from the animals own constituents. Although the immune response is a major defense against foreign substances which can cause disease, it cannot distinguish between helpful and harmful foreign substances and destroys both. During the last decade, an understanding of immunopathological reactions has greatly evolved as a result of the characterization of cytokines and interleukins which regulate ir_τ .fractions between cells of the immune system and other nonimmune tissues and cells such as endothelial cells, fibroblasts and adipocytes. A major cytokine increasingly recognized as a central mediator in a wide spectrum of physiologic and immune functions is macrophage-derived Tumor Necrosis Factor-α, also known as TNF- , or Cachectin. TNF- has been found to mediate effects as diverse as tumoricidal activity, wasting and weight loss associated with chronic disease, promotion of cartilage erosion and the destruction of joints in rheumatoid arthritis, and the recruitment of cells to participate more effectively in the host's response to an invasive agent. In addition, an increasingly large body of evidence indicates that TNF-α serves as the proximal mediator in the evolution of septic shock. The biological function of TNF-α extends well beyond its initial discovery as a mediator of tumor necrosis. It is increasingly realized that the interacting milieu of host cytokines existing locally and systemically is an extremely important network that dictates the pathogenesis of many immune and inflammatory diseases. TNF-α appears to play a critically important role in this regard because of its ability to activate a wide range of cell types in order to promote production of several key cytokines (e.g. IL-lβ, IL- lα and IL-6), bioactive eicosanoids, and platelet activating factor (PAF). Enhanced synthesis and release of cytokines has been observed during many acute and chronic inflammatory processes, and it is increasingly realized that in many cases, overproduction of TNF-α is a major contributor to inflammation, cellular injury, and cell death associated with various immunological based diseases. There are certain situations, such as with an allogeneic transplant or in "graft versus host" disease, where it would be extremely useful to suppress the immune response in order to prevent the rejection of helpful foreign tissue or organs. Allogeneic tissues and organs are tissues and organs from a genetically different member of the same species. "Graft versus host" disease occurs where the transplanted tissue, for example in a bone marrow transplant, contains allogeneic T-cells of the donor which cause an immune response against the recipient's own tissues. Although both humoral and cell-mediated immune responses play a role in the rejection of allogeneic tissues and organs, the primary mechanism involved is the cell- mediated immune response. Suppression of the immune response, and in particular, suppression of cell-mediated immune response, would thus be useful in preventing such rejection of allograft tissues and organs. For example, cyclosporin A is currently used as an immunosuppressive agent in the treatment of patients receiving allogeneic transplants and in "graft versus host" disease. There are times when the individual's immunological response causes more damage or discomfort than the invading microbes or foreign material, as- in the case of allergic reactions. Suppression of the immune response in these cases would be desirable. Occasionally, the immunological mechanisms become sensitized to some part of the individual's own body causing interference with or even destruction of that part. The ability to distinguish between "self" and "not self" is impaired and the body begins to destroy itself. This cε- res' lt in an autoimmune diseases such as rheumatoid an itis, insulin-dependent diabetes mellitus (which involves the autoimmune destruction of the β-cells of the islets of Langerhans which are responsible for the secretion of insulin), certain hemolytic anemias, rheumatic fever, thyroiditis, ulceractive colitis, myestheniagravis, glomerulonephritis, allergic encephalo-myelitis, continuing nerve and liver destruction which sometimes follows viral hepatitis, multiple sclerosis and systemic lupus erythematosus. Some forms of autoimmunity come about as the result of trauma to an area usually not exposed to lymphocytes such as neural tissue or the lens of the eye. When the tissues in these areas become exposed to lymphocytes, their surface proteins can act as antigens and trigger the production of antibodies and cellular immune responses which then begin to destroy those tissues. Other autoim une diseases develop after exposure of the individual to antigens which are antigenically similar to, that is cross-react with, the individual's own tissue. Rheumatic fever is an example of this type of disease in which the antigen of the streptococcal bacterium which causes rheumatic fever is cross-reactive with parts of the human heart. The antibodies cannot differentiate between the bacterial antigens and the heart muscle antigens and cells with either of those antigens can be destroyed. Suppression of the immune system in these autoimmune diseases would be useful in minimizing or eliminating the effects of the disease. Certain of these autoimmune diseases, for example, insulin-dependent diabetes mellitus, multiple sclerosis and rheumatoid arthritis, are characterized as being the result of a cell-mediated autoimmune response and appear to be due to the action of T-cells [See Sinha et al. Science 248, 1380 (1990)]. Others, such as rnyestheniagravis and systemic lupus erythematosus, are characterized as being the result of a humoral autoimmune response [ Id. ] . Suppression of the immune response would thus be useful in the treatment of patients suffering from autoimmune diseases. More particularly, suppression of cell-mediated immune response would thus be useful in the treatment of patients suffering from autoimmune diseases due to the action of T-cells such as insulin-dependent diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Suppression of humoral immune response would be useful in the treatment of patients suffering from T-cell independent autoimmune diseases such as rnyestheniagravis and systemic lupus erythematosus. SUMMARY OF THE INVENTION The present invention provides compounds having the formula ( I) : formula (I wherein X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR wherein R is C^C,, alkyl or hydrogen; Z is hydrogen or NH 2 ; and n is the integer 1 or 2; or a pharmaceutically acceptable salt thereof. In addition the present invention provides compounds having the formula (II): wherein Xi and X 2 are each independently hydrogen or OH; or a pharmaceutically acceptable salt thereof. The present invention further provides a process for preparing a compound of the formula (III) OH formula (III) wherein X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR; R is C 1 ~C 4 alkyl or hydrogen; and Z is hydrogen or NH 2 , comprising reacting a compound of formula (IV) formula (IV) wherein Q is NH 2 , halogen or ORi wherein Ri is Cχ-C alkyl; X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR; R is ~ ι~Cn alkyl or hydrogen; and Z is hydrogen or NH 2 ; with a suitable AMP deaminase. In addition the invention provides a process for the enantiomeric enrichment of a compound of formula (III) comprising reacting a racemic mixture of a compound of formula (IV) with a suitable AMP deaminase. The present invention also provides a method of effecting immunosuppression in a patient in need thereof comprising administering to said patient an effective immunosuppressive amount of a compound of formulas (I) or (II). The present invention also provides a method of suppressing adaptive immunity in a patient in need thereof comprising administering to said patient an effective immunosuppressive amount of a compound of formulas (I) or (II). DETAILED DESCRIPTION OF THE INVENTION As used herein the term "C 1 -C 4 alkyl" refers to a saturated straight or branched chain hydrocarbon radical of one to four carbon atoms. Included within the scope of this term are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and the like. The term "halogen" or "halo" refers to a chlorine, bromine or iodine atom. The term "Pg" refers to a protecting group such as isopropyldimethylsilyl, tert-butyldiphenylsilyl, methyl-di- tert-butylsilyl , tert-butyldimethylsilyl, benzyl, p- methoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p- chlorobenzyl, triphenylmethyl, methoxymethyl, 2- methoxyethoxymethyl, acetate and benzoate. The term "Lg" refers to a leaving group such as methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, 2- nitrobenzenesulfonate, 3-nitrobenzenesulfonate, 4- nitrobenzenesulfonate or 4-bromobezenesulfonate and the like. It is understood in the art that a protecting group can function as a leaving group and a leaving group can function as a protecting group depending upon the reaction conditions utilized. The terms "Ms" or "mesylate" refers to a methanesulfonate functionality of the formula: O -CH 3 O The terms "Ts", "Tos" or "tosylate" refers to a p- toluenesufonate functionality of the formula: The term "stereoisomer" refers to a compound made up of the same atoms bonded by the same bonds but having 0 different three-dimensional structures which are not interchangeable. The three dimensional structures are called configurations. The term "enantiomer" refers to two sterioiso ers whose _5 molecules are nonsuperimposable mirror images of one another . The term "racemic mixture" or "racemic modification" refers to a mixture of equal parts of enantiomers. 0 The term "chiral center" refers to a carbon atom to which four different groups are attached. The terms "enantiomeric excess" or "ee" refers to the 5 percent by which one enantiomer, Ei, is in excess in a mixture of the two enantiomers, Ei plus E 2 , such that; (E l " E 2 ) x 100% = ee (Ei + E 2 ) 0 The term "suitable AMP deaminase" refers to an enzyme that converts a compound of formula (IV) to the racemic mixture or enantiomerically enriched 6-oxo-nucleoside of formula (III) at a temperature of about 10 to 30°C in about 35 40 minutes to 7.5 days. The preferred suitable AMP deaminase is adenosine monophosphate deaminase (AMPDA; EC 3.5.4.6) isolated from Aspergillus sp. which is commercially available from Sigma and from Amano (as Deamizyme 5000). The term "pharmaceutically acceptable salt" refers to those salts that are not substantially toxic at the dosage administered to achieve the desired effect and do not independently possess significant pharmacological activity. The salts included within the scope of this term are hydrobromide, hydrochloride, sulfuric, phosphoric, nitric, formic, acetic, propionic, succinic, glycolic, lactic, malic, tartaric, citric, ascorbic, α-ketoglutaric, glutamic, aspartic, maleic, hydroxymaleic, pyruvic, phenylacetic, benzoic, p-aminobenzoic, anthranilic, p- hydroxybenzoic, salicyclic, hydroxyethanesulfonic, ethylenesulfonic, halobenzenesulfonic, toluenesulfonic, naphthalenesulfonic, methanesulfonic, sulfanilic, and the like. Such salts can exist in either a hydrated or substantially anhydrous form. Hydrochloride is preferred as the pharmaceutically acceptable salt of compounds of formulas (I) and (II). It is understood that the compounds of formulas (I), (II), (II) and (IV) may exist in a variety of stereoisomeric configurations. It is further understood that these compounds may exist in either tautomeric form. For example, compounds of formula (I) also can exist as the tautomer decribed by formula (I'). formula (I) formula (I ' ) The stereoisomeric configurations and the tautomers of the compounds of formulas (I), (II), (II) and (IV) are included within the scope of this invention. It is further understood that where the relative configuration is fixed, the maximum number of enantiomers possible for each compound is equal to 2 n wherein n represents the total number of chiral centers located on the compound. The enantiomers of formulas (I), (II), (III) and (IV) are included within the scope of this invention. The starting material for preparation of compounds of formula (I) wherein X is N 3 , NHR, N(R) 2 , CN, SH or SR can be prepared as described in Scheme I. The initial starting material for use in Scheme I defined by structure (1) wherein Q is NH , C 1 -C 4 alkoxy or halogen and all other substituents are as previously defined can be prepared by chemical reactions analogously known in the art, such as that disclosed by Borcherding et al. in European Patent Application Publication No. 0 475 411 published March 18, 1992, European Patent Application Publication No. 0 475 413 published March 18, 1992 and European Patent Application Publication No. 0 545 413 published June 9, 1993. In addition compounds of formula (1) wherein Z is NH 2 and Q is chlorine can be prepared following the procedure described by Halazy, S., et al. Nucleosides and Nucleotides, 11(9), 1595 (1992). All other substituents, unless otherwise indicated, are previously defined. The reagents and starting materials are readily available to one of ordinary skill in the art. Sche e I In Scheme I, step A the 3 '-hydroxy derivative of formula (1) is treated with a suitable sulfonyl chloride to provide the sulfonate derivative described by formula (2). For example, the 3'-hydroxy derivative of formula (1), such as (1R,3S)-cis-l-(9-adenyl)-hydroxycyclopentane is dissolved in a suitable organic solvent mixture, such as methylene chloride and tetrahydrofuran (5:3). An excess of a suitable sulfonyl chloride is added. Examples of a suitable sulfonyl chloride are methanesulfonyl chloride, trifluoromethanesulfonyl chloride, p-toluenesulfonyl chloride, 2-nitrobenzenesulfonyl chloride, 3- nitrobenzenesulfonyl chloride, 4-nitrobenzenesulfonyl chloride or 4-bromobezenesulfonyl chloride. The preferred sulfonyl chloride is methanesulfonyl chloride. Triethylamine is added and the reaction is stirred for 30 minutes to 3 hours. The reaction is then quenched with water and extracted with a suitable organic solvent, such as methylene chloride. The combined organic extracts are dried over a suitable drying agent, such as anhydrous sodium sulfate, filtered and concentrated under vacuum to provide the sulfonate derivative described by formula (2). In Scheme I, step B the sulfonate derivative of formula (2) can undergo a nucleophillic substitution by treatment with a suitable nucleophile to provide the compounds described by formula (3). For example, a sulfonate derivative of formula (2), such as (1R, 3S)-cis-l-(9-adenyl)-3- ethanesulfoxycyclopentane is dissolved in a suitable organic solvent, such as ethanol, dimethylsulfoxide or dimethylformamide and treated with an excess of a suitable nucleophile. Examples of suitable nucleophiles include sodium azide, sodium cyanide, potassium cyanide, lithium cyanide, methylamine, dimethylamine, methyl mercaptide, sodium hydrosulfide, sodium 2-dimethylamino-l-ethoxide, potassium phthalimide, potassium thioacetate and the like. The reaction is stirred at room temperture for approximately 24 hours and then heated at reflux for 2 to 6 hours. Alternatively the reaction can be directly heated at reflux for 2 to 6 hours. The reaction is then concentrated under vacuum and the residue is purified by techniques well known to one skilled in the art. For example, the residue is dissolved in a suitable organic solvent mixture, such as methylene chloride:methanol (9:1) and passed through a plug of silica gel. The filtrate is then concentrated under vacuum to provide the nucleophilic substitution product described by formula (3). The starting material for compounds of formula (I) wherein X is CH 2 NH 2 , C0 2 H, CONH 2 and CH 2 OH and n=l can be prepared as described in Scheme II. All other substituents, unless otherwise indicated, are previously defined. The reagents and starting materials are readily available to one of ordinary skill in the art. Scheme I I In Scheme II, optional step A the cyno compound (prepared in Scheme I wherein X is CN) described by formula (4) is reduced to the appropriately substituted aminomethyl compound described by formula (5). For example, the cyano compound described by formula (4), such as 1R,3R-trans-l-( 9-adenyl)-3-cyanocyclopentane, is dissolved in a suitable solvent, such as tetrahydrofuran and treated with an excess of a suitable reducing agent, such as 2M aluminum hydride in tetrahydrofuran. The reaction is refluxed for 2 to 6 hours. Excess reducing agent is carefully decomposed by treatment with acetone and then acidified to pH 7. The mixture is then filtered and the filtrate is concentrated under vacuum. The residue is purified by techniques well known to one skilled in the art. For example, the residue is purified by flash chromatography on silica gel with methylene chloride:methanol (17:3) as eluent to provide the (1R,3R)- trans-1-(9-adenyl)-3-aminomethylcyclopentane described by formula (5) . In Scheme II, optional step B the cyano compound described by formula (4) is hydrolyzed to the appropriately substituted amide described by formula (6). For example, the cyano compound described by formula (4), such as (1R, 3R)-trans-1-(9-adenyl)-3-cyanocyclopentane is dissolved in a suitable solvent, such as methanol and treated with an equivalent of a suitable base, such as potassium hydroxide. The reaction is heated at reflux for 1 to 5 hours and then concentrated under vacuum. The residue is then purified by techniques well known in the art. For example the residue can be purified by flash chromatography on silica gel utilizing a suitable eluent, such as methylene chloride:methanol to provide the purified amide ( 6) . In Scheme II, optional step C the cyano compound described by formula (4) is hydrolyzed to the appropriately substituted acid described by formula (7). For example, the cyano compound described by formula (4), such as ( 1R, 3R)-trans-1-(9-adenyl)-3-cyanocyclopentane is dissolved in a suitable organic solvent, such as tetrahyrofuran. An excess of a suitable base, such as potassium hydroxide is added and the reaction is heated at reflux for approximately 6 hours. After cooling, the reaction is neutralized with a suitable acid, such as 6N hydrochloric acid and the product purified by techniques well known to one skilled in the art. For example, the product can be isolated by ion exchange chromatography to provide the ( lR,3R)-trans-l-(9-adenyl)cyclopentane-3- carboxylic acid described by structure (7). In Scheme II, step D the carboxylic acid described by formula (7) is reduced to the appropriately substituted alcohol described by formula (8). For example, the carboxylic acid described by formula (7), such as (1R, 3R)-trans-1-(9-adenyl)cyclopentane-3- carboxylic acid is dissolved in a suitable organic solvent, such as tetrahyrofuran. An excess of a suitable reducing agent, such as 2M lithium aluminum hydride in tetrahydrofuran is added dropwise to the reaction. The reaction is heated at reflux for 2 to 6 hours. After cooling, excess reducing agent is decomposed by treatment with acetone followed by dilute hydrochloric acid to adjust to pH 7. The mixture is then filtered and the filtrate is concentrated under vacuum. The residue is then purified by techniques well known to one skilled in the art. For example, the residue can be purified by flash chromatography using methylene chloride:methanol (17:3) as the eluent to provide the (lR,3R)-trans-l-(9-adenyl)-3- hydroxymethylcyclopentane described by structure (8). The starting material for the compounds of the formula (I) wherein n=l and X is NH 2 can be prepared as described in Scheme III. All other substituents, unless otherwise indicated, are previously defined. The reagents and starting materials are readily available to one of ordinary skill in the art. Scheme III In Scheme III, the azide described by formula (9) (prepared in Scheme I, step B wherein X is N 3 ) is reduced to the primary amine described by formula (10). For example, the azide described by formula (9), such as (lR,3R)-trans-l-(9-adenyl)-3-azidocyclopentane is dissolved in a suitable organic solvent, such as tetrahydrofuran and treated with an excess of a suitable reducing agent, such as 2M lithium aluminum hydride in tetrahydrofuran. The reaction is heated at reflux for 2 to 6 hours. After cooling, the excess reducing agent is decomposed with water, the mixture is filtered and the filtrate is concentrated under vacuum. The residue is then purified by techniques well known to one skilled in the art. For example, the residue is purified by flash chromatography using silica gel and a suitable organic eluent, such as methylene chloride:methanol (17:3) to provide the (IR, 3R)-trans-l-(9-adenyl)-3-aminocyclopentane described by formula (10). The compounds of formula (III) can be prepared as described in Scheme IV. All substituents, unless otherwise indicated, are previously defined. The starting material required for the preparation of compounds of formula (III) is defined by formula (IV). The preparation of compounds of formula (IV) is described generally in Schemes (I), (II) and (III) and is encompassed by formulas (3) through (10). Additional reagents and starting materials are readily available to one of ordinary skill in the art. Scheme IV formula (IV) formula (III) In Scheme IV, compounds of formula (IV) can be treated with AMPDA to produce the 6-oxo-nucleoside described by formula (III) . For example, a compound of formula (IV) is added to a suitable solvent, such as 0.1M phosphate buffer (pH 6.5) followed by addition of 0.5 to 1.0 equivalents by weight of AMPDA (AMP deaminase from Aspergillus sp. , 0.096 unit/mg solid) . The reaction is then stirred at a temperature of about 10 to 30°C for aoout 40 minutes to 7.5 days. The product is then isolated and purified by techniques well known in the art. For example, the crude reaction mixture is lyophilized and the residue is purified by flash chromatography (15% methanol/methylene chloride, silica gel) to provide the 6-oxo-nucleoside of formula (I). In addition to the procedure described in Scheme IV compounds of formula (I) can be prepared as described in Scheme V, following generally the procedure described by Halazy, S. et al., Nucleosides and Nucleotides, 11(9), 1595 (1992). The starting material and reagents are previously described or are readily available to one of ordinary skill in the art. Scheme V formula (I) For example, a compound of formula (11) is combined with IN aqueous hydrochloric acid and a suitable organic solvent, such as tetrahydrofuran in a ratio of about 4:1 (v:v). The mixture is heated for about 10 hours at about 80°C. The product is then isolated by techniques well known in the art. For example the reaction is concentrated under vacuum and the residue is dissolved in a suitable solvent, such as hot water. After cooling, the product is collected by filtration to provide the 6-oxo-nucleoside of formula (I). Compounds of formula (I) wherein n=2 can be prepared in a manner analogous to that described in Scheme V following the procedure of Halazy, S. et al., Nucleosides and Nucleotides, 11(9), 1595 (1992) utilizing the 6- chloronucleoside of structure (12) as the starting material . The compounds of structure (12) can be prepared- following analogously the procedures described in Schemes I, II, III and V wherein the cis or trans isomers of 2- amino-6-chloro-9-(3-hydroxycyclohexyl)purine [prepared following the procedure of Halazy, S. et al., Nucleosides and Nucleotides, 11(9), 1595 (1992)] are initially substituted for formula (1) in Scheme I. The the starting material for the compounds of formula (II) can be prepared as described in Scheme VI. The products (16), (17) and (18) are subjected to conditions analogous to that previously described in Scheme V to provide the compounds of formula (II). All substituents, unless otherwise indicated, are previously defined. The reagents and starting materials are readily available to one of ordinary skill in the art. Scheme VI 18 17 16 In Scheme VI step A, 2-amino-6-chloropurine (13) is treated with a suitable base, such as sodium hydride in a suitable organic solvent such as dimethylformamide. An equivalent of the tosylate (14) [see Wolff-Kugel, D, et al., Tetrahedron Lett. , 32, 6341 (1991)] dissolved in dimethylformamide is added and the reaction is stirred for about 23 hours at about 50°C. The coupled product (15) is then isolated by techniques well known in the art. For example the reaction is concentrated under vacuum and the residue is purified by flash chromatography on silica gel with a suitable eluent, such as methanol/chloroform to provide coupled product (15). In Scheme VI step B, the coupled product (15) is subjected to a hydroboration-oxidation reaction to provide the trans-hydroxy compound (16). For example, the coupled product (15) is dissolved in a suitable solvent, such as tetrahydrofu"an and cooled to about 0°C under an inert atmosphere, such as argon. A solution of borane dimethylsulfide in tetrahydrofuran is added and the reaction is allowed to stir for about 18 hours at about 20°C. Then an excess of N-methyl morpholine-N-oxide is added in portions and the reaction is stirred for about 4.5 hours at about 40°C. The product is then isolated by technique-" well known in the art. For example the reaction is concentrated under vacuum and the residue purified by flash chromatography on silica gel with a suitable eluent, such as methanol/chloroform to provide the trans-hydroxy compound (16) . In Scheme VI step C, the coupled product (15) is subjected to an epoxidation-epoxide ring opening reaction to provide the trans-dihydroxy compound (17). For example the coupled product (15) is suspended in water at about 0°C and an excess of an epoxidation reagent, such as metachloroperbenzoic acid (MCPBA) is added in portions to the reaction with stirring. The reaction is then stirred at about 20°C for 1 hour and a suitable acid, such as 10% sulfuric acid is added. The reaction is then stirred for about 5 hours. The product is isolated by techniques well known in the art. For example the reaction is quenched with a suitable base, such as sodium bicarbonate, concentrated under vacuum and purified by flash chromatography on silica gel with a suitable eluent, such as methonal/chloroform to provide the trans-dihydroxy compound (17) . In Scheme VI step D, the coupled product (15) is subjected to a dihydroxylation reaction to prodvide the cis-dihydroxy compound (18). For example, the coupled product (15) is suspended in a suitable solvent mixture such as water/acetone. N-methylmorpholine-N-oxide and a suitable hydroxylation reagent, such as osmium tetroxide is added to the reaction. The reaction is stirred for about 2 hours at about 70°C. After cooling, the product is isolated by techniques well known in the art. For example the reaction is concentrated under vacuum and the residue is purified by flash chromatography on silica gel with a suitable eluent such as methanol/chloroform to provide after recrystallization from a suitable solvent, such as methanol the cis-dihydroxy compound (18). Treatment of the products of Scheme VI, compounds (16; (17) and (18), in a manner analogous to that described previously in Scheme V provides the compounds of formula (II). The various stereoisomers encompassed by formulas (I) and (II) are readily prepared by one skilled in the art. In addition to the enzymatic resolution of compounds of formula (III) by a suitable .AMP deaminase, the enantiomers of formulas (I) and (II) can be resolved utilizing techniques well known in the art such as crystallization techniques described by Jacques, J. et al. in Enantiomers, Racemates, and Resolutions, John Wiley and Sons, Inc., 1981 or by chiral column chromatography. The following examples present typical syntheses as described by Schemes I through VI. These examples are understood to be illustrative only and are not intended to limit the scope of the invention in any way. As used in the following examples, the following terms have the meanings indicated: "eq." refers to equivalents, "g" refers to grams, "mg" refers to milligrams, "mmol" refers to millimoles, "mL" refers to milliliters, "°C" refers to degrees Celsius, "TLC" refers to thin layer chromatography, and "δ" refers to parts per million down field from tetramethylsilane. Preparation of IR, 3S-cis-l-(9-adenyl )-3- methanesulfoxycyclopentane. Scheme I, step A; Dissolve ( IR, 3S)-cis-l-(9-adenyl)-3- hydroxycyclopentane (150 mg, 0.7 mmol) in methylene chloride (15 mL) and tetrahydrofuran (9 mL) . Add excess methanesulfonyl chloride and triethylamine and stir for 30 minutes. Add water (50 mL) and separate the layers. Extract the aqueous phase with methylene chloride (50 mL), combine the organic phases and dry over anhydrous sodium sulfate. Filter and concentrate to provide (IR,3S)-cis-1- (9-adenyl)-3-methanesulfoxycyclopentane (190 mg) as a white solid. Preparation of (IR, 3R)-trans-1-( 6-hydroxy-purin-9-yl)-3- azidocyclopentane. Scheme I, step B; Dissolve ( IR,3S)-cis-1-(9-adenyl)- 3-methanesulfoxycyclopentane (170 mg, 0.6 mmol) and lithium azide (60 mg, 1.2 mmol) in ethanol (10 mL). Stir overnight at room temperature and then reflux for three hours. Concentrate the reaction under vacuum and purify the residue by dissolving it in a mixture of methylene chloride:methanol (9:1) and then passing the solution through a silica gel plug. Concentrate the filtrate under vacuum to provide (IR,3R)-trans-l-( 9-adenyl)-3- azidocyclopentane (120 mg) as a white solid, mp 109.5-110°C; IR (azide, 2100.61 cm -1 ); [α] D =-16.8° (c=0.519, methanol); UV=261 nm (H 2 0) ; CI/MS (CH 4 ) 245 (M +1 ), 202 (base); 13 C NMR (DMSO-d 6 ) 6 156, 152, 149, 139, 119, 61, 53, 38, 30, 29; 1 H NMR (DMSO-d 6 ) δ 8.22 (s, 1H) , 8.16 (s, 1H) , 7.2 (bs, 2H, exch. D 2 0), 5.02 (p, 1H) , 4.48 (m, 1H) , 2.56-2.0 (m, 5H) , 1.75 (m, 1H). Scheme IV; Combine ( IR, 3S)-cis-l-(9-adenyl)-3- azidocyclopentane (100 mg) and 0.IM phospate buffer (30 mL) with stirring. Add AMPDA (100 mg, AMP deaminase from Aspergillus sp.; 0.096 units/mg solid) and stir the reaction at room temperature until no starting material remains as indicated by TLC or HPLC. Lyophilize the reaction and purify the residue by flash chromatography (15% methanol/methylene chloride, silica gel) to provide the title compound. Preparation of ( IR, 3R)-trans-1-( 6-hydroxy-purin-9-yl)-3- cyanocyclopentane . Scheme I, step B; Dissolve ( IR,3S)-cis-1-(9-adenyl)-3- methanesulfoxycyclopentane (0.6 mmol) and potassium cyanide (1.2 mmol) in dimethylsulfoxide. Heat the reaction at 75°C for 6 hours and then concentrate under vacuum. Purify in a manner analoguous to example 2a to provide (lR,3R)-trans-l J - (9-adenyl)-3-cyanocyclopentane. Scheme IV; In an analogous manner to Example 2 Scheme IV the title compound can be prepared from (IR,3R)-trans-l- (9-adenyl)-3-cyanocyclopentane and AMPDA. Example 4 Preparation of (IR,3R)-trans-l-(6-hydroxy-purin-9- yl)cyclopentane-3-thiol. Scheme I , step B; Dissolve (IR,3S)-cis-l-(9-adenyl)-3- methanesulfoxycyclopentane (0.6 mmol) and sodium hydrogensulfide (1.2 mmol) in ethanol. Reflux the reaction for three hours and then concentrate under vacuum. Purify in a manner analoguous to example 2 to provide (1R,3R)- trans-l-(9-adenyl)cyclopentane-3-thiol . Scheme IV; In an analogous manner to Example 2 Scheme IV the title compound can be prepared from (lR,3R)-trans-l- (9-adenyl)cyclopentane-3-thiol. Preparation of (IR,3R)-trans-l-( 6-hydroxy-purin-9-yl)-3-N- methylaminocyclopentane. Scheme I, step B; Dissolve (IR,3S)-cis-l-(9-adenyl)-3- methanesulfoxycyclopentane (0.6 mmol) and methylamine (1.2 m ol) in ethanol. Reflux the reaction for three hours and then concentrate under vacuum. Purify in a manner analoguous to example 2 to provide (IR,3R)-trans-1-(9- adenyl)-3-N-methylaminocyclopentane. Scheme IV; In an analogous manner to Example 2 Scheme IV the title compound can be prepared from (IR,3R)-trans-l- (9-adenyl)-3-N-methylaminocyclopentane and AMPDA. Preparation of (IR,3R)-trans-l-(6-hydroxy-purin-9-yl)-3- N,N-dimethylaminocyclopentane. Scheme I, step B; Dissolve (IR,3S)-cis-l-(9-adenyl)-3- methanesulfoxycyclopentane (0.6 mmol) and dimethylamine (1.2 mmol) in ethanol. Reflux the reaction for three hours and then concentrate under vacuum. Purify in a manner analoguous to example 2 to provide (IR,3R)-trans-1-(9- adenyl)-3-N,N-dimethylaminocyclopentane. Scheme IV; In an analoguous manner to Example 2 Scheme IV the title compound can be prepared from (IR,3R)-trans-l- (9-adenyl)-3-N,N-dimethylaminocyclopentane and AMPDA. Example 7 Preparation of (IR,3R)-trans-l-(6-hydroxy-purin-9-yl)-3- methylmercaptocyclopentane. Scheme I, step B; Combine (IR,3S)-cis-l-(9-adenyl)-3- methanesulfoxycyclopentane (0.6 mmol) and potassium hydroxide (1.2 mmol) in methanol. Bubble in methyl mercaptan until the solution is saturated and then reflux for three hours. Concentrate the reaction under vacuum and purify in a manner analoguous to example 2 to provide (IR,3R)-trans-1-(9-adenyl)-3-methylmercaptocyclopentane. Scheme IV; In an analogous manner to Example 2, Scheme IV the title compound can be prepared from (IR,3R)-trans-l- (9-adenyl)-3-methylmercaptocyclopentane and AMPDA. Example 8 Preparation of (lR,3R)-trans-l-(6-hydroxy-purine-9-yl)-3- aminomethylcyclopentane. Scheme I, step B; Dissolve (lR,3S)-cis-l-(9-adenyl)-3- cyanocyclopentane in tetrahydrofuran and add excess 2M lithium aluminum hydride in tetrahydrofuran dropwise. Reflux for two to six hours. Decompose the excess lithium aluminum hydride, filter and concentrate under vacuum. Purify the residue by flash chromatography (silica gel) using methylene chloride:methanol (17:3) as the eluent to provide (IR, 3R)-trans-l-(9-adenyl)-3-aminomethylcyclo- pentane. Scheme IV; In an analogous manner to Example 2, Scheme IV the title compound can be prepared from ( IR, 3R)-trans-1- (9-adenyi)-3-aminomethylcyclopentane and AMPDA. Example 9 OH Preparation of (IR,3R)-trans-l-(6-hydroxy-purin-9- yl)cyclopentane-3-carboxamide. Scheme I, step B; Dissolve IR, 3S-cis-l-(9-adenyl )-3- cyanocyclopentane (1 mmol) in methanol and treat with potassium hydroxide (1 mmol). Heat the reaction at reflux for 2 hours. After cooling concentrate under vacuum and purify the residue by flash chromatography (methylene chloride/methanol, 17:3, silica gel) to provide (1R,3R)- trans-1-(9-adenyl)cyclopentane-3-carboxamide. Scheme IV; In an analogous manner to Example 2, Scheme IV the title compound can be prepared from (IR,3R)-trans-l- (9-adenyl)cyclopentane-3-carboxamide and AMPDA. Example 10 Preparation of (IR, R)-trans-l-(6-hydroxy-purin-9- yl)cyclopentane-3-carboxylic acid. Scheme I, step C; Dissolve (IR,3S)-cis-1-(9-adenyl)-3- cyanocyclopentane in tetrahydrofuran and add excess potassium hydroxide. Reflux for approximately 6 hours. Neutralize the reaction with 6N hydrochloric acid and purify by ionexchange chromatography to provide (1R,3R)- trans-l-(9-adenyl)cyclopentane-3-carboxylic acid. Scheme IV; In an analogous manner to Example 2, Scheme IV the title compound can be prepared from (IR,3R)-trans-l- (9-adenyl)cyclopentane-3-carboxylic acid and AMPDA. Example 11 OH Preparation of ( lR,3R)-trans-l-(6-hydroxy-purin-9-yl)-3- hydroxymethylcyclopentane. Scheme I, step B; Dissolve (IR,3R)-trans-1-(9- adenyl)cyclopentane-3-carboxylic acid in tetrahydrofuran and add excess 2M lithium aluminum hydride in tetrahydrofuran dropwise. Reflux for two to six hours. Decompose the excess lithium aluminum hydride, filter, concentrate under vacuum and purify in a manner analogous to example 9 to provide (IR, 3R)-trans-l-( 9-adenyl)-3- hydroxymethylcyclopentane. Scheme IV; In an analogous manner to Example 2, Scheme IV the title compound can prepared from ( IR, 3R)-trans-1-(9- adenyl)-3-hydroxymethylcyclopentane and AMPDA. Example 12 Preparation of ( IR,3R)-trans-l-( 6-hydroxy-purin-9-yl)-3- aminocyclopentane. Scheme IV; Dissolve (IR,3R)-trans-1-(9-adenyl)-3- azidocyclopentane in tetrahydrofuran and add excess 2M lithium aluminum hydride in tetrahydrofuran dropwise. Reflux for two to six hours. Decompose the excess lithium aluminum hydride, filter, concentrate under vacuum and purify in a manner analogous to example 9 to provide (lR,3R)-trans-l-(9-adenyl)-3-aminocyclopentane. Scheme IV; In an analogous manner to Example 2, Scheme IV the title compound can prepared from ( IR,3R)-trans-l-(9- adenyl)-3-aminocyclopentane and AMPDA. Example 13 OH Preparation of (IR,3R)-( trans)-9-(3- hydroxycyclopentyl)quanosine. The (lR,3R)-l-[9 (2,6-diaminopurine) ]-3-hydroxycyclopentane starting material is prepared utilizing known prior art techniques. For example, suspend diaminopurine sulfate hydrate (16g, 60 mmol) in dry dimethylformamide (150 mL) and add sodium hydride (60% dispersion, 5.7 g, 180 mmol). Stir the reaction for 2 hours at 60°C. Then add (lS,3R)-3- acetoxy-1-methanesulfonyloxycyclopentane (4.4 g, 20 mmol in 50 mL of dimethylformamide). Stir the reaction at 60°C for 48 hours. Distill off the solvent and extract the residue with methylene chloride. Wash the organic with water, brine, dry over anhydrous sodium sulfate, filter and concentrate under vacuum. Purify the residue by flash chromatography (silica gel, methylene chloride/methanol, 9:1) to provide (IR,3R)-1-[9( 2,6-diaminopurine) ]-3- acetoxycyclopentane (2.3 g). Dissolve the (1R,3R)-1- [9( 2,6-diaminopurine) ]-3-acetoxycyclopentane (1.8 g) in methanol/water (44:1), add potassium carbonate (2.6 g) and stir the reaction for 1 hour at room temperature. Then filter the reaction, concentrate the filtrate under vacuum and purify the residue by flash chromatography (silica gel, methylene chloride/methanol, 9:1 - _• provide (1R,3R)-1- [9 ( 2,6-diaminopurine) ]-3-hydroxyc_ lopentane (1.3 g), mp 193.5°C. Scheme IV; In an analogous manner to Exampel 2 Scheme IV the title compound can prepared from (IR,3R)-l-[9 ( 2,6- diaminopurine) ]-3-hydroxycyclopentane and AMPDA; [ ] D = _ 7.31 (c=0.471, methanol). Example 14 The above 2-amino-6-chloro-9-( 3- hydroxycyclopentyl)purines can be prepared following the procedure of Halazy, S, et al., Nucleosides and Nucleotides, 11(9), 1595 (1992). Suspend 2-amino-6-chloro- purine (5 g, 29.5 mmol) and cyclopentene-2-one (10 g, 119 mmol) in anhydrous DMF (50 mL) under an atmosphere of argon. Cool the reaction to 20°C and add 1,8- diazabicyclo[5.4.0 ]undec-7-ene (250 mg, DBU) with stirring. After 48 hours concentrate the reaction under vacuum. Suspend the residue in ethanol (100 mL) and cool to -15°C. Add sodium borohydride (1.5 g, 40 mmol) in portions and stir the reaction at 20°C for 20 hours. Add excess acetone containing acetic acid to quench the reaction. Concentrate the mixture under vacuum and purify the residue by flash chromatography (silica gel, chloroform/methanol) to provide the (+)-(trans)-2-amino-6-chloro-9-( 3-hydroxycyelopentyl)- purine (1.4 g, a) and the (I) (±)-(cis)-2-amino-6-chloro-9- (3-hydroxycyclopentyl)purine (3.6 g, b) . Example 15 Preparation of (+)-( trans)-9-( 3- hydroxycyclopentyl)quanosine. Scheme IV;In an analogous manner to Example 2 Scheme IV the title compound can be prepared from trans-2-amino-6- chloro-9-(3-hydroxycyclopentyl)purine (prepared in example 14) and AMPDA. Alternative procedure for preparation of (±)-( trans)-9- ( 3-hydroxycyclopentyl)guanosine. Scheme V; Dissolve (±)-(trans)-2-amino-6-chloro-9-( 3- hydroxycyclopentyl)purine (5.7 mmol, prepared in example 14) in IN aqueous hydrochloric acid (10 mL) and tetrahydrofuran (2.5 mL) . Heat the solution at 80°C for 10 hours and then concentrate under vacuum. Dissolve the residue in hot water and then cool. Collect the solid by filtration to provide the title compound; 1 H NMR (D 2 O) δ 8.8 (s, 8H), 5.1 (m, IH), 4.65(m, IH) , 2.5(m, IH) , 2.3(m, 2H) , 2.05(m, IH), 1.8(m, IH) . Example 16 OH Preparation of (+)-(cis)-9-( 3-hydroxycyclopentyl)quanosine, Scheme IV; In an analogous manner to Example 2 Scheme IV the title compound is prepared from (±)-(cis)-9-( 3- hydroxycyclopentyl)guanosine (prepared in example 14) and AMPDA. Alternative procedure for preparation of (±)-(cis)-9- ( 3-hydroxycyclopentyl)guanosine. Scheme V; Dissolve (±)-(cis)-2-amino-6-chloro-9-( 3- hydroxycyclopentyl)purine (5.7 mmol, prepared in example 14) in IN aqueous hydrochloric acid (10 mL) and tetrahydrofuran (2.5 mL) . Heat the solution at 80°C for 10 hours and then concentrate under vacuum. Dissolve the residue in hot water and then cool. Collect the solid by filtration to provide the title compound; X H NMR (D 2 0) δ 8.85 (s, 8H), 5.0 (m, IH) , 4.5(m, IH) , 2.6(m, IH) , 2.45(m, IH), 2.2(m, IH), 2.0(m, 2H) . Example 17 Preparation of ( +)-( trans)-9-[ 3- hydroxycyclopentyl)methylJguanosine (16) . Scheme VI step A; Add 2-amino-6-chloropurine (10 g, 59 mmol) portionwise to a vigorously stirred suspension of sodium hydride (2.36 g of a 60% dispersion washed with hexane) in dimethylformamide (100 mL) at 20°C under argon. Stir for 30 minutes and add the tosylate (14) [14.86 g, 59 mmol; see Wolff-Kugel, D, et al. Tetrahedron Lett., 32, 6341 (1991)] dissolved in dimethylformamide (20 mL) . Stir the reaction at 50°C for 23 hours. Then concentrate the reaction under vacuum and purify the residue by flash chromatography (silica gel, methanol/chloroform) to provide 8.14 g of the coupled product (15). Scheme VI step B; Dissolve the coupled product (15) (2.49 g, 10 mmol) in anhydrous tetrahydrofuran (15 mL) under argon. Cool the solution to 0°C and slowly add a ION solution of borane dimethylsulfide in 2 mL of tetrahydrofuran. Stir the reaction for 18 hours at 20°C and then add N-methylmorpholine-N-oxide (4.05 g, 30 mmol) in portions. Stir the reaction at 40°C for 4.5 hours. Then concentrate the reaction under vacuum and purify the residue by flash chromatography (silica gel, methanol/chloroform) to provide the trans-hydroxy compound (16). General procedure of Scheme V; Dissolve the trans- hydroxy compound (16) (1.52 g, 5.7 mmol) in IN aqueous hydrochloric acid (10 mL) and tetrahydrofuran (2.5 mL) and heat the reaction at 80°C for 10 hours. After cooling, concentrate the reaction under vacuum and dissolve the residue in hot water. After cooling, collect the product by filtration to provide the title compound (1.15 g); 1 H NMR (DMSO-d 6 ) δ 12.0(s, IH), 9.35(s, 8H), 7.5(m, 2H), 4.3 (m, IH), 4.1(d, 2H), 2.8(m, IH), 1.25-1.95(m, 6H) . Example 18 OH Preparation of (+)-(cis,trans)-9-[3,4- dihydroxycyclopentyl)methyl .guanosine (17) . Scheme VI step C; Suspend the coupled product (15) (0.747 g, 3 mmol, prepared in example 17, step A) in water (20 mL) . Cool the suspension to about 0°C and add portionwise metachloroperbenzoic acid (1.14 g, 3.3 mmol, MCPBA) . Stir the reaction for 1 hour at 20°C and add 10% sulfuric acid (0.5 mL) . Stir the reation for 5 hours at 20°C then cool the reaction to 0°C and quench with sodium bicarbonate. Concentrate the reaction under vacuum and purify by flash chromatography (silica gel, methanol/chorloform) to provide 0.33 g of the trans-hydroxy compound ( 17 ) . General procedure of Scheme V; In a manner analogous to that described in example 16 the title compound is obtained in 70% yield from the trans-hydroxy compound (17); X H NMR (D 2 0) δ 7.85(s, 8H), 4.1(d, 2H) , 4.05(m, 2H), 2.7(m, IH), 2.2(m, IH), 1.8(m, IH) , 1.7(m, .) , 1.3 (m, IH) . Example 19 OH OH Preparation of (+)-( trans, trans)-9-[ 3 ,4- 5 dihydroxycyclopentyl)methyl.guanosine (18) . Scheme VI step D; Suspend the coupled product (15) (1 g, 4 mmol, prepared in example 17, step . in water (5 mL) and acetone (15 mL) . Add N-methylmorpholine-N-oxide (0.6 g, 4.4 mmol) and osmium tetroxide (12 mg). Stir the ° reaction at 70oC for 2 hours. Concentrate the reaction under vacuum and purify the residue by flash chromatography (silica gel, methanol/chloroform) to provide 1.0 g of the cis-hydroxy compound (18). 5 General procedure of Scheme V; In a manner analogous to that described in example 17 the title compound is obtained in 80% yield from the trans-hydroxy compound (18); X H NMR (DMSO-d 6 ) δ 10.7(s, IH), 7.85(s, 8H) , 6.55(s, 2H) , 4.45(s, 2H), 4.0(m, 2H) , 3.9(d, 2H) , 2.75(m, IH) , 1.4-1.8 0 (m, 4H). 5 Exampie 20 OH Preparation of (+)-(cis)-9-( 3-hydroxycyclohexyl)guanosine. The (lα, 3α)-2-amino-6-chloro-9-( 3- hydroxycyclohexyl)purine (3.35 g) is prepared in a manner analogous the the procedure described in example 14 from DBU (150 mg), 2-amino-6-chloropurine (3 g, 17.75 mmol), cyclohexanone (4 g) and sodium borohydride (1 g). General procedure of Scheme V; In a manner analogous to that described in example 17 the title compound is obtained in 72% yield from the (±)-(cis)-2-amino-6-chloro- 9-(3-hydroxycyclohexyl)purine as described by Halazy, S. et al. Nucleosides and Nucleotides, 11(9), 1595 (1992); 1 H NMR (D 2 0) δ 8.85(s, 8H), 4.5(m, IH) , 3.85(m, IH) , 2.5(d, IH) , 1.3-2.2(m, 7H). Example 21 OH Preparation of (+)-( trans)-9-( 3- hydroxycyclohexyl)guanosine. The (±)-(trans)-2-amino-6-chloro-9-(3- hydroxycyclohexyl)purine (150 mg) is prepared in a manner analogous the the procedure described in example 14 from DBU (150 mg), 2-amino-6-chloropurine (3 g, 17.75 mmol), cyclohexanone (4 g) and sodium borohydride (1 g). General procedure of Scheme V; In a manner analogous to that described in example 17 the title compound is obtained from the (±)-(trans)-2-amino-6-chloro-9-(3- hydroxycyclohexyl)purine as described by Halazy, S. et al , Nucleosides and Nucleotides, 11(9), 1595 (1992). The present invention further provides a method of effecting immunosuppression, and more specifically, a method of suppressing adaptive immunity, in a patient in need thereof comprising administering to said patient an effective immunosuppressive amount of a compound of formulas (I) or (II). As used herein, the term "patient" refers to a warm¬ blooded animal such as a mammal which is suffering from a disease, such as an autoimmune disease or "graft versus host" disease, or is in danger of rejection of a transplanted allogeneic tissue or organ. It is understood that humans, mice and rats are included within the scope of the term "patient". Administration of a compound of formulas (I) or (II) to a patient results in an immunosuppressive effect in the patient. More specifically, administration of a compound of formulas (I) or (II) to a patient results in suppression of adaptive immunity in the patient. In other words, by treatment of a patient with a compound of formulas (I) or (II), the adaptive immune response of the patient is inhibited or suppressed over that present in the absence of treatment. A patient is in need of treatment with an immunosuppressive agent, such as a compound of formulas (I) or (II), where the patient is suffering from an autoimmune disease, "graft versus host" disease or in order to prevent rejection of transplanted allogeneic tissues or organs. The term "autoimmune disease" refers to those disease states and conditions wherein the immune response of the patient is directed against the patient's own constituents resulting in an undesirable and often terribly debilitating condition. Patients suffering from autoimmune diseases such as rheumatoid arthritis, insulin-dependent diabetes mellitus, certain hemolytic anemias, rheumatic fever, thyroiditis, septic shock syndrome, ulceractive colitis, rnyestheniagravis, glomerulonephritis, allergic encephalo- myelitis, continuing nerve and liver destruction which sometimes follows viral hepatitis, multiple sclerosis and systemic lupus erythematosus are in need of treatment with an immunosuppressive agent such as a compound of formulas (I) or (II). Rheumatoid arthritis, insulin-dependent diabetes mellitus and multiple sclerosis are characterized as being the result of a cell-mediated autoimmune response and appear to be due to the action of T-cells. Myestheniagravis and systemic lupus erythematosus are characterized as being the result of a humoral autoimmune response. As such, treatment of patients suffering from these diseases by administration of a compound of formulas (I) or (II) will be particularly effective in preventing further deterioration or worsening of the patient's condition. Treatment of a patient at an early stage of an autoimmune disease, such as rheumatoid arthritis, insulin- dependent diabetes mellitus, multiple sclerosis, myestheniagravis or systemic lupus erythematosus, would be particularly effective in preventing further deterioration of the disease state into a more serious condition. For example, insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease which is believed to result from the autoimmune response directed against the β-cells of the islets of Langerhans which secrete insulin. Treatment of a patient suffering from an early stage of IDDM prior to the complete destruction of the β-cells of the islets of Langerhans would be particularly useful in preventing further progression of the disease since it would prevent or inhibit further destruction of remaining insulin-secreting β-cells. It is understood that treatment of a patient suffering from an early stage of other autoimmune diseases will also be particularly useful to prevent or inhibit further natural progression of the disease state to more serious stages. Patients who have received or who are about to receive an allogeneic tissue or organ transplant, such as an allogeneic kidney, liver, heart, skin, bone marrow, are also patients who are in need of prophylactic treatment with an immunosuppressive agent such as a compound of formulas (I) or (II). An immunosuppressive agent will prevent the adaptive immune response of the donee from rejecting the allogeneic tissue or organ of the donor. Likewise, patients suffering from "graft versus host" disease are patients who are in need of treatment with an immunosuppressive agent such as a compound of formulas (I) or (II). An immunosuppressive agent will prevent the adaptive immune response of the transplanted tissue or organ from rejecting the allogeneic tissue or organ of the donee. Based on standard clinical and laboratory tests and procedures, an attending diagnostician, as a person skilled in the art, can readily identify those patients who are in need of treatment with an immunosuppressive agent such as a compound of formulas (I) or (II). An effective immunosuppressive amount of a compound of formulas (I) or (II) is that amount which is effective, upon single or multiple dose administration to a patient, in providing an immunosuppressive effect or, more particularly, a suppression of adaptive immune response. An immunosuppressive effect refers to the slowing, interrupting, inhibiting or preventing the further expression of the adaptive immune response. An effective immunosuppressive amount of a compound of formulas (I) or (II) can be readily determined by the attending diagnostician, as one skilled in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount or dose, a number of factors are considered by the attending diagnostician, including, but not limited to: the species of mammal; its size, age, and general health; the specific disease involved; the degree of or involvement or the severity of the disease; the response of the individual patient; the particular compound administered; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances. An effective immunosuppressive amount of a compound of formulas (I) or (II) is expected to vary from about 0.1 milligram per kilogram of body weight per day (mg/kg/day) to about 500 mg/kg/day. Preferred amounts are expected to vary from about 1 to about 50 mg/kg/day. In effecting treatment of a patient, a compound of formulas (I) or (II) can be administered in any form or mode which makes the compound bioavailable in effective amounts, including oral and parenteral routes. For example, compounds of formulas (I) or (II) can be administered orally, subcutaneously, intramuscularly, intravenously, transdermally, intranasally, rectally, and the like. Oral administration is generally preferred. One skilled in the art of preparing formulations can readily select the proper form and mode of administration depending upon the particular characteristics of the compound selected the disease state to be treated, the stage of the disease, and other relevant circumstances. The compounds can be administered alone or in the form of a pharmaceutical composition in combination with pharmaceutically acceptable carriers or excipients, the proportion and nature of which are determined by the solubility and chemical properties of the compound selected, the chosen route of administration, and standard pharmaceutical practice. The compounds of the invention, while effective themselves, may be formulated and administered in the form of their pharmaceutically acceptable acid addition salts for purposes of stability, convenience of crystallization, increased solubility and the like. In another embodiment, the present invention provides compositions comprising a compound of formulas (I) or (II) in admixture or otherwise in association with one or more inert carriers. These compositions are useful, for example, as assay standards, as convenient means of making bulk shipments, or as pharmaceutical compositions. An assayable amount of a compound of formulas (I) or (II) is an amount which is readily measurable by standard assay procedures and techniques as are well known and appreciated by those skilled in the art. Assayable amounts of a- compound of formulas (I) or (II) will generally vary from about 0.001% to about 75% of the composition by weight. Inert carriers can be any material which does not degrade or otherwise covalently react with a compound of formulas (I) or (II). Examples of suitable inert carriers are water; aqueous buffers, such as those which are generally useful in High Performance Liquid Chromatography (HPLC) analysis; organic solvents, such as acetonitrile, ethyl acetate, hexane and the like; and pharmaceutically acceptable carriers or excipients. More particularly, the present invention provides pharmaceutical compositions comprising an effective immunosuppressive amount of a compound of formulas (I) or (II) in admixture or otherwise in association with one or more pharmaceutically acceptable carriers or excipients. The pharmaceutical compositions are prepared in a manner well known in 'the pharmaceutical art. The carrier or excipient may be a solid, semi-solid, or liquid material which can serve as a vehicle or medium for the active ingredient. Suitable carriers or excipients are well known in the art. The pharmaceutical composition may be adapted for oral or parenteral use, including topical use, and may be administered to the patient in the form of tablets, capsules, suppositories, solution, suspensions, or the like. The compounds of the present invention may be administered orally, for example, with an inert diluent or with an edible carrier. They may be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the compounds may be incorporated with excipients and used in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, chewing gums and the like. These preparations should contain at least 4% of the compound of the invention, the active ingredient, but may be varied depending upon the particular form and may conveniently be between 4% to about 70% of the weight of the unit. The amount of the compound present in compositions is such that a suitable dosage will be obtained. Preferred compositions and preparations according to the present invention are prepared so that an oral dosage unit form contains between 5.0-300 milligrams of a compound of the invention. The tablets, pills, capsules, troches and the like may also contain one or more of the following adjuvants: binders such as microcrystalline cellulose, gum tragacanth or gelatin; excipients such as starch or lactose, disintegrating agents such as alginic acid, Primogel, corn starch and the like; lubricants such as magnesium stearate or Sterotex; glidants such as colloidal silicon dioxide; and sweetening agents such as sucrose or saccharin may be added or a flavoring agent such as peppermint, methyl salicylate or orange flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as polyethylene glycol or a fatty oil. Other dosage unit forms may contain other various materials which modify the physical form of the dosage unit, for example, as coatings. Thus, tablets or pills may be coated with sugar, shellac, or other enteric coating agents. A syrup may contain, in addition to the present compounds, sucrose as a sweetening agent and certain preservatives, dyes and colorings and flavors. Materials used in preparing these various compositions should be pharmaceutically pure and non-toxic in the amounts used. For the purpose of parenteral therapeutic administration, including topical administration, the compounds of the present invention may be incorporated into a solution or suspension. These preparations should contain at least 0.1% of a compound of the invention, but may be varied to be between 0.1 and about 50% of the weight thereof. The amount of the inventive compound present in such compositions is such that a suitable dosage will be obtained. Preferred compositions and preparations according to the present invention are prepared so that a parenteral dosage unit contains between 5.0 to 100 milligrams of the compound of the invention. The solutions or suspensions may also include the one or more of the following adjuvants: sterile diluents such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylene diaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. The parenteral preparation can be enclosed in ampules, disposable syringes or multiple dose vials made of glass or plastic. As • ith any group of structurally related compounds which possesses a particular generic utility, certain groups and configurations are preferred for compounds of formula (I) in their end-use application. Compounds of the formula (I) wherein Z is NH 2 are generally preferred. The following list illustrates compounds according to the present invention: 1) (lR,3R)-(trans)-l-(6-hydroxy-purin-9-yl)-3- azidocyclopentane; 2) (1R,3R) (trans)-9-(3-hydroxycyclopentyl)guanosine; 3) (+)-(trans)-9-(3-hydroxycyclopentyl)guanosine; 4) (+)-(cis)9-(3-hydroxycyclopentyl)guanosine; 5) (+)-(trans)-9-[3- hydroxycyclopentyl)methyl . guanosine; 6) (+)-(cis,trans)-9-[3,4- dihydroxycyclopentyl)methyl]guanosine; 7) (+)-(trans,trans)-9-[3,4- dihydroxycyclopentyl)methyl]guanosine; 8) (±)-(cis)-9-(3-hydroxycyclohexyl)guanosine; 9) (+)-(trans)-9-(3-hydroxycyclohexyl)guanosine. The following studies illustrate the utility of the compounds of formulas (I). These studies are understood to be illustrative only and are not intended to limit the scope of the invention in any way. As used herein the following terms have the indicated meanings: "μM" refers to micromolar concentration; "Units" refers to the internationally accepted measurement of protein; "S.D." refers to standard deviation; "ηmol" refers to nanomoles; "ηg" refers to nanograms; "μg" refers to micrograms. Inhibition of Lipopolysaccharide-induced Production of Tumor Necrosis Factor-α in Human Macrophages Utilizing an in vitro cellular immunology-based assay which uses human peripheral blood and subsequent purification of monocyte-derived macrophages (according to the method of Edwards et al. J. Cellular Biochemistry 1993, 19E: 35), (IR,3R)-(trans)-9-( 3-hydroxycyclopentane)- guanosine showed activity in proinflammatory cytokine inhibition. Monocyte-derived macrophages stimulated with a lethal dose (1.0 μg/ml) bacterial lipopolysaccharide (LPS) produce high levels of TNF-α (14.9 ηg/mL) during 18 hours of culture. (IR, 3R)-(trans)-9-(3-hydroxycyclopentane)- guanosine was effective at inhibiting TNF-α levels in a dose response fashion in concentrations ranging from 500 μM to 0.001 μM in comparison to the positive control of treatment with LPS only. The results are summarized in Table 1. Table 1. Concentration of (1 R,3R)-(trans)-9-(3- hydroxycyc.opentane.-guanosine Percentage Inhibition 500μg 57.4 100μg 31.6 10μg 17.5 5μg 4.8 1 μg 0 0.1 μg 12.1 0.01 μg 0 0.001 μg 9.67 Inhibition of Lipopolysaccharide-induced Production of Interluekin-lβ in Human Macrophages Utilizing an in vitro cellular immunology-based assay which uses human peripheral blood and subsequent purification of monocyte-derived macrophages (according to the method of Edwards et al. J. Cellular Biochemistry 1993, 19E: 35), (IR,3R)-(trans)-9-( 3-hydroxycyclopentane)- guanosine showed activity in proinflammatory cytokine inhibition. Monocyte-derived macrophages stimulated with a lethal dose (1.0 ηg/ml) bacterial lipopolysaccharide (LPS) produce high levels of Interleukin-lβ as assayed by (14.7 ηg/mL) during 18 hours of culture. ( IR,3R)-( trans)-9-(-3- hydroxycyclopentane) uanosine was effective at inhibiting IL-lβ levels over concentrations ranging from 500 μM to 0.001 μM in comparison to the positive control of treatment with LPS only. The results are summarized in Table 2. Table 2 Concentration of (1 R,3R) -(trans)-9-(-3- hydroxycyclopentane)guanosine Percentage Inhibition 500μg - 100μg 31.0 10μg 22.3 5μg 18.6 i μg 5.5 0.1 μg 33.8 0.01 μg 28.9 0.001 μg 27.6 In Vivo Protection from Lipopolysaccharide-induced Death Activity Utilizing an in υiυo immunology-based assay which uses a D-galactosamine animal model of septic shock (according to the method of Parmely et al . European Cytokine Network, 3(2):249 (1992), ( IR,3R)-( trans)-9-( 3-hydroxycyclo- pentane)guanosine showed elevated activity in protecting mice against the lethal effects of LPS. Mice treated with the vehicle Hanks Balanced Salt Solution (HBSS) approximately 1 hour before intraperitoneal (i.p.) challenge of 18 mg D-galactosamine and 25 ηg LPS, succumbed to disease by 9 hours after challenge (e.g., 6 out of 6 mice killed). However, mice treated with ( IR,3R)-( trans )- 9-( 3-hydroxycyclopentane)guanosine (100 mg/kg i.p., time = -1 hour) were afforded significantly enhanced protection (2 out of 6 mice killed; 66% protection).

Claims: WHAT IS CLAIMED IS: 1. A compound of the formula OH wherein X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR; R is C^C,, alkyl or hydrogen; Z is hydrogen or NH 2 ; and n is the integer 1 or 2; or a pharmaceutically acceptable salt thereof. 2. A compound of the formula wherein Xi and X 2 are each independently hydrogen or OH? or a pharmaceutically acceptable salt thereof. 3. The compound according to claim 1 wherein n is the integer 1. 4. The compound according to claim 3 wherein Z is hydrogen. 5. The compound according to claim 4 wherein X is N 3 . 6. The compound according to claim 1 wherein the compound is IR,3R-( trans)-l-(6-hydroxy-purin-9-yl)-3- azidocyclopentane. 7. The compound according to claim 1 wherein the compound is ( IR,3R)-(trans)-9-(3-hydroxycyclopentyl)- guanosine. 8. The compound according to claim 1 wherein the compound is (±)-(trans)-9-( 3-hydroxycyclopentyl)guanosine. 9. The compound according to claim 1 wherein the compound is ( )-(cis)-9-(3-hydroxycyclopentyl)guanosine. 10. The compound according to claim 1 wherein the compound is (+)-(cis)-9-(3-hydroxycyclohexyl)guanosine. 11. The compound according to claim 1 wherein the compound is (+)-(trans)-9-( 3-hydroxycyclohexyl)guanosine. 12. The compound according to claim 2 wherein the compound is (+;)-( trans)-9-[3-hydroxycyclopentyl)- methyl]guanosine. 13. The compound according to claim 2 wherein the compound is (+)-(cis, trans)-9-[ 3,4-dihydroxycyclopentyl)- methyl]guanosine. 14. The compound according to claim 2 wherein the compound is (÷)-(trans, trans)-9-[ 3,4-dihydroxycyclopentyl) • methyl]guanosine. 15. A process for preparing a compound of the formula comprising reacting a compound of the formula OH wherein X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR; R is C 1 ~C 4 alkyl or hydrogen; and Z is hydrogen or NH 2 , comprising reacting a compound of the formula wherein Q is NH 2 , halogen or ORi wherein Ri is Cχ-C alkyl; X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , C0NH 2 , C0 2 H, CH 2 OH, SH or SR; R is C^C^ alkyl or hydrogen;- and Z is hydrogen or NH 2 ; with a suitable AMP deaminase. 16. The process according to claim 15 wherein Z is hydrogen. 17. The process according to claim 16 wherein X is N 3 . 18. A method of effecting immunosuppression in a patient in need thereof comprising administering to a patient an effective immunosuppressive amount of a compound selected from formula (1) wherein X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR; R is C 1 ~C 4 alkyl or hydrogen; Z is hydrogen or NH 2 ; and n is the integer 1 or 2; or from formula (2) wherein Xi and X 2 are each independently hydrogen or OH; or a pharmaceutically acceptable salt thereof. 19. A method of suppressing adaptive immunity in a patient comprising administering to a patient in need thereof an effective immunosuppressive amount of a compound selected from formula (1) wherein X is OH, N 3 , NH 2 , NHR, N(R) 2 , CN, CH 2 NH 2 , CONH 2 , C0 2 H, CH 2 OH, SH or SR; R is λ -C A alkyl or hydrogen; Z is hydrogen or NH 2 ; and n is the integer 1 or 2; or from formula (2) wherein Xi and X 2 are each independently hydrogen or OH; or a pharmaceutically acceptable salt thereof. 20. The method according to claim 19 wherein the compound is (1R,3R)-(trans)-9-( 3-hydroxycyclopentyl)- guanosine. 21. The method according to claim 19 wherein the patient is in need of treatment for allograft rejection, 22. The method according to claim 19 wherein the patient is in need of treatment for an autoimmune disease. 23. The method according to claim 22 wherein the autoimmune disease is insulin-dependent diabetes mellitus 24. The method according to claim 22 wherein the autoimmune disease is multiple sclerosis. 25. The method according to claim 22 wherein the autoimmune disease is rheumatoid arthritis. 26. The method according to claim 22 wherein the autoimmune disease is myestheniagravis. 27. The method according to claim 22 wherein the autoimmune disease is systemic lupus erythematosus. 28. The method according to claim 22 wherein the autoimmune disease is septic shock syndrome.

Inventors: BORCHERDING DAVID R, EDWARDS CARL K III, EGGENSPILLER ANNE, HALAZY SERGE, MARGOLIN ALEXEY L, BORCHERDING, DAVID, R., EDWARDS, CARL, K., III, EGGENSPILLER, ANNE, HALAZY, SERGE, MARGOLIN, ALEXEY, L.
Applicants: MERRELL DOW PHARMA, MERRELL DOW PHARMACEUTICALS INC.
Application year: 1994
Main classification: C07D473
IPC codes: A61K31, A61P1, A61P3, A61P7, A61P13, A61P15, A61P21, A61P29, A61P37, C07D473